The Federal Womens Study is an active clinical protocol aimed at recruiting 360 federal employees and contractors working in the Washington DC metropolitan area. One hundred and forty-nine (149) women (50% African-American, 15% African immigrant and 35% white) have been screened (age 4310, range 24-62 years). Among the enrolled women, the three groups are well matched by race/ethnicity for key socio-economic and demographic risk factors such as educational attainment, family history of diabetes and physical activity. Yet, we have already identified pre-diabetes in 30% of women (53% African-American, 5% African immigrant and 43% white). Therefore, this cohort reflects women who are at high risk for diabetes and heart disease and an excellent group in which to (a) test the efficacy of existing screening tests and (b) understand the pathophysiological progression of cardiometabolic disease. Since current cardiometabolic screening tests are centered on triglyceride and fasting glucose concentrations, we have employed two approaches to examine these risk factors. Relationship of Triglycerides with Insulin Resistance and Hepatic Fat Content by Race/ Ethnicity In black women, fasting triglyceride concentrations are paradoxically normal in the presence of insulin resistance and increased risk for diabetes. The reasons for this paradoxical relationship is unclear but may be related to decreased ectopic fat in the visceral and hepatic compartments. In this study we compared by race and continent of origin, the relationship of triglyceride concentration to key cardiometabolic risk factors, specifically diet, physical activity, insulin resistance (and hyperinsulinemia) and hepatic fat content. Consistent with our hypothesis, fasting triglyceride and triglyceride-rich lipoprotein concentrations are comparable in African immigrant and African American women and lower than in white women (P<0.01). Daily physical activity and dietary fatty acid profiles were similar (P>0.1) Lower fasting triglyceride-rich lipoproteins were independently related to lower visceral and a marker of de novo lipogenesis (adjR2=0.37, P<0.001). These findings were presented at nationally at the American Diabetes Association Scientific Sessions in June 2018 and the manuscript is in preparation. Relationship of Insulin resistance and Triglycerides with Postprandial Hyperinsulinemia by Race/ Ethnicity Postprandial hyperinsulinemia may be an important cardiometabolic risk factor to help explain the paradoxical relationship of triglycerides with insulin resistance, as noted above. To evaluate the contribution of insulin secretion, insulin clearance and prandial gut factors to race/ethnic differences in hyperinsulinemia and insulin resistance, we compared insulin response to oral, intravenous and prandial glucose loads. Black (African immigrant and African American) pre- and post-menopausal women black higher insulin response that was related to lower insulin clearance (P<0.01) but similar levels of insulin resistance and insulin secretion rates. Lower insulin clearance was associated with lower triglyceride concentrations and lower hepatic fat content. These analyses help to elucidate important pathophysiological pathways that increase diabetes risk in women of African ancestry and provide additional evidence that screening and diagnostic diabetes guidelines should be population-specific. These findings were presented nationally at the American Diabetes Association Scientific Sessions in June 2018 and the manuscript is under review at the Journal of Clinical Endocrinology and Metabolism (August 2018). Novel screening paradigms To evaluate novel screening paradigms, we compared the diagnostic ability of two morphological features of the glucose curve (time to glucose peak and glucose curve) as prediabetes risk prediction tools. Using a multiple-sample 2hour oral glucose tolerance test (OGTT), we showed that the glucose peak parameter maximized the information gained from a single OGTT without increasing the time commitment of the participants - and was a strong independent indicator of pancreatic beta cell function. This work was recognized nationally (oral presentation at Endocrine Society Annual meeting in 2017) and by media outlets and is published in the journal of Clinical Endocrinology. Our findings support the need for larger validation studies of the time to glucose peak parameter, especially in communities with a combination of high population risk for diabetes and limited resources. In short, this multi-ethnic/race study of women has the potential based on current publications, manuscripts under review and manuscripts in draft form to impact approaches to early detection and prevention of diabetes and cardiovascular disease worldwide.